The Saupe matrix describing protein alignment in a liquid crystalline medium contains five independent elements, enabling the generation of up to five linearly independent alignment conditions. Measurement of internuclear residual dipolar couplings (RDCs) by NMR spectroscopy under these conditions, orthogonal in five-dimensional alignment space, provides access to the amplitude, asymmetry, and direction of motions of the internuclear vector. In collaboration with Michael F. Summers (HHMI, U. of Maryland BC) we developed a technique applicable to the structure of large retroviral RNA structures, which can measure the RDCs for adenine H2-N1 and H2-N3 interactions at a high degree of precision. and to identify the structure-function relationship to viral packaging. Application to a 36-nucleotide RNA showed excellent agreement with its accurately known structure, validating the method. Applied to a 78 kD Rev response element from the HIV-1 virus, which has an effective rotational correlation time of ca 160 ns, the method yields sensitivity gains of more than an order of magnitude over previously published methods.